Project Summary Cardiac surgery has been a highly innovative field of medicine. The introduction of major innovations, and ongoing incremental change in existing ones, have extended survival and improved quality of life for many patients suffering from cardiac disease. A rapid pace of innovation requires a rigorous infrastructure for clinical evaluation that provides timely assessments of the value of new and modified treatments. The Cardiothoracic Surgical Trials Network (CTSN) was created to provide a rigorous evidence base tor the surgical treatment of cardiothoracic disease. The International Center for Health Outcomes and Innovation Research (InCHOIR) enthusiastically embraces the opportunity to continue to work in partnership with clinical investigators and the NIH as the CTSN DCC. The Network has developed a rich research agenda for the renewal that includes trials of novel neuroprotective agents, long-term antithrombotic strategies, new regenerative medicine therapies, and surgical approaches to valvular disease, heart failure and atrial fibrillation. Given our long-standing interest and experience in the design and analysis of cardiac surgery multicenter studies, we are in a strong position to serve as the coordinating center for this vital clinical research effort. In particular, we will provide leadership in designing novel trials that optimize sample size, include patient- centered as well as clinical endpoints, and collect data from a variety of sources, including electronic data capture systems, mobile apps and wearable sensors, registries and electronic health records. We have a strong track record of obtaining efficient regulatory approval for our trials from the FDA and Health Canada, training and monitoring sites nationally and internationally, ensuring robust enrollment and retention, data management and quality assurance, data sharing, and overall administrative coordination. We have the infrastructure to expand our trials to include mechanistic studies that use biospecimens collected and managed through the CTSN biorepository. Finally, the DCC plays an important role in the analysis, interpretation and dissemination of research findings. We will continue to support the process of publishing in high-impact journals that should lead to revision of practice guidelines and to surgical practice itself. This goal should be further optimized by incorporating Implementation Science approaches into Network trials, which should decrease the well-recognized gap between publication of trial results and adoption of findings into widespread practice.